Evaluation of the WHO 2010 Grading and AJCC/UICC Staging Systems in Prognostic Behavior of Intestinal Neuroendocrine Tumors

<div><p>Background</p><p>The increasing incidence and heterogeneous behavior of intestinal neuroendocrine tumors (iNETs) pose a clinicopathological challenge. Our goal was to decribe the prognostic value of the new WHO 2010 grading and the AJCC/UICC TNM staging systems for iNETs. Moreover, outcomes of patients treated with somatostatin analogs were assessed.</p><p>Methods</p><p>We collected epidemiological and clinicopathological data from 93 patients with histologically proven iNETs including progression and survival outcomes. The WHO 2010 grading and the AJCC/UICC TNM staging systems were applied for all cases. RECIST criteria were used to define progression. Kaplan-Meier analyses for progression free survival (PFS) and overall survival (OS) were performed.</p><p>Results</p><p>Mean follow-up was 58.6 months (4–213 months). WHO 2010 grading yielded PFS and disease-specific OS of 125.0 and 165.8 months for grade 1 (G1), 100.0 and 144.2 months for G2 and 15.0 and 15.8 months for G3 tumors (p = 0.004 and p = 0.001). Using AJCC staging, patients with stage I and II tumors had no progression and no deaths. Stage III and IV patients demonstrated PFS of 138.4 and 84.7 months (p = 0.003) and disease-specific OS of 210.0 and 112.8 months (p = 0.017). AJCC staging also provided informative PFS (91.2 vs. 50.0 months, p = 0.004) and OS (112.3 vs. 80.0 months, p = 0.005) measures with somatostatin analog use in stage IV patients.</p><p>Conclusion</p><p>Our findings underscore the complementarity of WHO 2010 and AJCC classifications in providing better estimates of iNETS disease outcomes and extend the evidence for somatostatin analog benefit in patients with metastatic disease.</p></div

Kaplan-Meier survival analyses and octreotide use.

<p>(<b>A</b>) PFS median estimates for AJCC stage IV patients treated or not with octreotide were 91.2 and 50.0 months respectively; N = 40 (p = 0.004). (<b>B</b>) OS median estimates for AJCC stage IV patients treated or not with octreotide were 112.3 and 80.0 months respectively; N = 40 (p = 0.005). (<b>C</b>) Disease-specific OS median estimates for AJCC stage IV patients treated or not with octreotide were 114.5 and 80.0 months respectively; N = 40 (p = 0.013).</p

Presence of distant metastases according to WHO grading and AJCC staging.

<p>(A) WHO classification - The proportion of distant metastases was significantly different according to WHO grading as follows: 12 (32.4%) of G1 cases, 21 (58.3%) of G2 cases and 3 (75.0%) of G3 cases; N = 77 (p = 0.030); (B) Proportion of cases in each stage of AJCC classification - All the 40 patients (100%) with distant metastases were classified at stage IV; N = 93 (p<0.001); (C) Disease progression - Cases with distant metastases were associated to disease progression in 29 (72.5%) patients vs. 9 (17.0%) of patients without distant metastases; N = 93 (p<0.001); (D) Deaths occurred in 14 (35.0%) of patients with distant metastases vs. 7 (13.2%) of patients without distant metastases; N = 93 (p = 0.013); (E) Disease-specific deaths occurred in 13 (32.5%) of patients with distant metastases vs. 2 (3.8%) of patients without distant metastases; N = 93 (p<0.001).</p

Kaplan-Meier survival analyses.

<p>(A) Progression free survival (PFS) according to WHO classification: Mean estimates were 107.6 months for G1, 99.8 months for G2 and 15.7 months for G3; N = 77 (p = 0.004). (B) Overall survival (OS) according to WHO classification: mean estimates were 161.4 months for G1, 140.6 months for G2 and 15.2 months for G3; N = 77 (p<0.001). (C) Disease-specific OS according to WHO classification: mean estimates were 165.8 months for G1, 144.2 months for G2 and 15.8 months for G3; N = 77 (p = 0.001). (D) PFS according to AJCC classification: median estimates were 70.0 months for stage I, 120.0 months for stage II, 138.4.0 months for stage III and 84.7 months for stage IV; N = 93 (p = 0.003). (E) OS according to AJCC classification: median estimates were 70.0 months for stage I, 120.0 months for stage II, 210.0 months for stage III and 110.4 months for stage IV; N = 93 (p = 0.320). (F) Disease-specific OS according to AJCC staging: median estimates were 70.0 months for stage I, 120.0 months for stage II, 210.0 months for stage III and 112.8 months for stage IV; N = 93 (p = 0.017).</p

WHO grading and AJCC staging analyses.

<p>Abbreviations: WHO, World Health Organization; AJCC/UICC, American Joint Committee on Cancer/Union Internationale Contre le Cancer; Dx, diagnosis; LN, lymph node; NA, not available; NS, non-significant.</p><p>Percentages reflect distribution among each grade or stage.</p

Additional file 1: of Molecular profiling of advanced solid tumors and patient outcomes with genotype-matched clinical trials: the Princess Margaret IMPACT/COMPACT trial

Supplementary methods and Tables S1–S4. (DOCX 148 kb